Early Injury Landscape in Vein Harvest by Single-Cell and Spatial Transcriptomics.

BACKGROUND: Vein graft failure following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. Although previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on vein graft failure. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. METHODS: Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing and spatial transcriptomics analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-carotid vein bypass implantation in a canine model (n=4). RESULTS: Spatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways (P<0.05) involved in the activation of endothelial cells (ECs), fibroblasts, and vascular smooth muscle cells, namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and ECM (extracellular matrix) remodeling throughout the vein wall. Subsequent single-nuclei RNA-sequencing analysis supported these findings and further unveiled distinct EC and fibroblast subpopulations with significant upregulation (P<0.05) of markers related to endothelial injury response and cellular activation of ECs, fibroblasts, and vascular smooth muscle cells. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including VCAN, FBN1, and VEGFC, in addition to novel genes of interest, such as GLIS3 and EPHA3. These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9. By integrating the spatial transcriptomics and single-nuclei RNA-sequencing data sets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and fibroblasts were notably enriched in the intima and media of distended veins. Finally, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal-transitioning ECs, protomyofibroblasts, and vascular smooth muscle cells in upregulating signaling pathways associated with cellular proliferation (MDK [midkine], PDGF [platelet-derived growth factor], VEGF [vascular endothelial growth factor]), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension. CONCLUSIONS: Vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.

Hemodynamics and Wall Mechanics of Vascular Graft Failure.

Blood vessels are subjected to complex biomechanical loads, primarily from pressure-driven blood flow. Abnormal loading associated with vascular grafts, arising from altered hemodynamics or wall mechanics, can cause acute and progressive vascular failure and end-organ dysfunction. Perturbations to mechanobiological stimuli experienced by vascular cells contribute to remodeling of the vascular wall via activation of mechanosensitive signaling pathways and subsequent changes in gene expression and associated turnover of cells and extracellular matrix. In this review, we outline experimental and computational tools used to quantify metrics of biomechanical loading in vascular grafts and highlight those that show potential in predicting graft failure for diverse disease contexts. We include metrics derived from both fluid and solid mechanics that drive feedback loops between mechanobiological processes and changes in the biomechanical state that govern the natural history of vascular grafts. As illustrative examples, we consider application-specific coronary artery bypass grafts, peripheral vascular grafts, and tissue-engineered vascular grafts for congenital heart surgery as each of these involves unique circulatory environments, loading magnitudes, and graft materials.

Predictors of amputation-free survival and wound healing after infrainguinal bypass with alternative conduits.

OBJECTIVE: Inadequate vein quality or prior harvest precludes use of autologous single segment greater saphenous vein (ssGSV) in many patients with chronic limb-threatening ischemia (CLTI). Predictors of patient outcome after infrainguinal bypass with alternative (non-ssGSV) conduits are not well-understood. We explored whether limb presentation, bypass target, and conduit type were associated with amputation-free survival (AFS) after infrainguinal bypass using alternative conduits. METHODS: A single-center retrospective study (2013-2020) was conducted of 139 infrainguinal bypasses performed for CLTI with cryopreserved ssGSV (cryovein) (n = 71), polytetrafluoroethylene (PTFE) (n = 23), or arm/spliced vein grafts (n = 45). Characteristics, Wound, Ischemia, and foot Infection (WIfI) stage, and outcomes were recorded. Multivariable Cox proportional hazards and classification and regression tree analysis modeled predictors of AFS. RESULTS: Within 139 cases, the mean age was 71 years, 59% of patients were male, and 51% of cases were nonelective. More patients undergoing bypass with cryovein were WIfI stage 4 (41%) compared with PTFE (13%) or arm/spliced vein (27%) (P = .04). Across groups, AFS at 2 years was 78% for spliced/arm, 79% for PTFE, and 53% for cryovein (adjusted hazard ratio for cryovein, 2.5; P = .02). Among cases using cryovein, classification and regression tree analysis showed that WIfI stage 3 or 4, age >70 years, and prior failed bypass were predictive of the lowest AFS at 2 years of 36% vs AFS of 58% to 76% among subgroups with less than two of these factors. Although secondary patency at 2 years was worse in the cryovein group (26% vs 68% and 89% in arm/spliced and PTFE groups; P < .01), in patients with tissue loss there was no statistically significant difference in wound healing in the cryovein group (72%) compared with other bypass types (72% vs 87%, respectively; P = .12). CONCLUSIONS: In patients with CLTI lacking suitable ssGSV, bypass with autogenous arm/spliced vein or PTFE has superior AFS compared with cryovein, although data were limited for PTFE conduits for distal targets. Despite poor patency with cryovein, wound healing is achieved in a majority of cases, although it should be used with caution in older patients with high WIfI stage and prior failed bypass, given the low rates of AFS.

Taurolidine irrigation reduces relapse and recurrence of hemodialysis access infection.

OBJECTIVES: Infection of hemodialysis access is a clinically important concern and can lead to increased morbidity and mortality among patients on hemodialysis. In this study, we aimed to determine whether using taurolidine as an irrigating antiseptic after drainage of pus or removal of infected tissue and graft during surgery decreases the relapse and recurrence of infection. METHODS: Between January 2016 and December 2023, 48 episodes in 38 patients hospitalized and treated for hemodialysis access infections were examined. Relapse, recurrence, and mortality of infection were analyzed in patients who received additional taurolidine irrigation versus those who did not. After drainage alone or after total or partial graft removal, all patients received massive irrigation with normal saline. The episodes of infection were examined consecutively during follow-up. RESULTS: The majority (97.9%) of hemodialysis access infections were arteriovenous grafts (AVGs) or interposed grafts from native veins. In AVGs, infections occurred primarily after a median of 523 days from the first needling. All prosthetic materials that were the infection foci were removed in 58.3% of the cases, with partial resection and bypass or drainage performed in the remaining cases. The most common pathogen was Staphylococcus aureus (45.8%). After surgical intervention, relapse was observed in 12.5% of the cases and recurrence in 20.8% of the cases. The relapse occurrence was significantly reduced by taurolidine irrigation (odds ratio [OR]: 0.16, 95% confidence interval [CI]: 0.02-0.98, p = 0.05) and the total resection of prosthetic material (OR: 0.07, 95% CI: 0.01-0.70, p = 0.02). Recurrence was significantly decreased by taurolidine irrigation (OR: 0.10, 95% CI: 0.02-0.56, p = 0.01) and increased dramatically in cases with relapse history (OR: 8.50, 95% CI: 1.69-42.76, p < 0.01). Finally, male sex (hazard ratio: 7.01, 95% CI: 1.19-41.40, p = 0.03) and AVG (hazard ratio: 4.49, 95% CI: 1.01-20.01, p = 0.05) were significantly associated with increased overall mortality in infected hemodialysis access. CONCLUSIONS: Additional taurolidine irrigation after surgical resection significantly reduced the relapse and recurrence of infection in hemodialysis access. Taurolidine appears to be a safe and useful antiseptic for the control of hemodialysis access infection.

Silica nanoparticles enhance interfacial self-adherence of a multi-layered extracellular matrix scaffold for vascular tissue regeneration.

PURPOSE: Based on the clinical need for grafts for vascular tissue regeneration, our group developed a customizable scaffold derived from the human amniotic membrane. Our approach consists of rolling the decellularized amniotic membrane around a mandrel to form a multilayered tubular scaffold with tunable diameter and wall thickness. Herein, we aimed to investigate if silica nanoparticles (SiNP) could enhance the adhesion of the amnion layers within these rolled grafts. METHODS: To test this, we assessed the structural integrity and mechanical properties of SiNP-treated scaffolds. Mechanical tests were repeated after six months to evaluate adhesion stability in aqueous environments. RESULTS: Our results showed that the rolled SiNP-treated scaffolds maintained their tubular shape upon hydration, while non-treated scaffolds collapsed. By scanning electron microscopy, SiNP-treated scaffolds presented more densely packed layers than untreated controls. Mechanical analysis showed that SiNP treatment increased the scaffold's tensile strength up to tenfold in relation to non-treated controls and changed the mechanism of failure from interfacial slipping to single-point fracture. The nanoparticles reinforced the scaffolds both at the interface between two distinct layers and within each layer of the extracellular matrix. Finally, SiNP-treated scaffolds significantly increased the suture pullout force in comparison to untreated controls. CONCLUSION: Our study demonstrated that SiNP prevents the unraveling of a multilayered extracellular matrix graft while improving the scaffolds' overall mechanical properties. In addition to the generation of a robust biomaterial for vascular tissue regeneration, this novel layering technology is a promising strategy for a number of bioengineering applications.

Inflow Artery Aneurysmal Degeneration After Long Term Native Arteriovenous Fistula for Haemodialysis.

OBJECTIVE: Inflow arterial aneurysms are a rare but serious complication after long term arteriovenous fistulae (AVF), probably due to arterial wall remodelling after an increase in flow and shear stress, and kidney transplantation with immunosuppressive therapy. This study aimed to describe the outcomes of surgical treatment and long term follow up in a large cohort. METHODS: This prospective cohort study collected data from patients with a true inflow artery aneurysm after AVF creation that was surgically repaired between 2010 and 2022. Anastomotic and infected aneurysms or post-puncture pseudoaneurysms were excluded. Demographic data, access characteristics, symptoms, treatment strategies, and long term follow up were recorded; patency was estimated using Kaplan-Meier survival analysis. RESULTS: During the study period, 28 patients (64% men, mean age 60.1 years) were treated surgically for aneurysmal degeneration of the axillary or brachial (n = 23) or radial (n = 5) artery after an AVF (10 distal, 18 proximal) performed a mean of 18.3 ± SD 7.9 years previously. Most AVFs were ligated or thrombosed, while all patients except one had previously received kidney transplants. Most of the cases (n = 18) were symptomatic: 13 with pain or swelling, four with distal embolisation, and one rupture. They were repaired by aneurysm partial excision and graft interposition (11 great saphenous vein, six ipsilateral basilic vein, three cephalic vein, and two PTFE graft), ligation (n = 3), or direct end to end anastomosis (n = 3). No major complications occurred before discharge, after a mean hospital stay of 2.4 days. After a mean follow up of 4.8 ± 3.3 years, three cases presented complications: two recurrent proximal brachial aneurysms were repaired with an additional proximal interposition graft (one with further late infected pseudoaneurysm) and an asymptomatic post-traumatic graft thrombosis. Five year primary and secondary patency was 84% and 96%, respectively. CONCLUSION: Aneurysmal degeneration of the inflow artery is an unusual complication during long term follow up of AVFs. Aneurysm excision and, in general, autogenous graft interposition using the saphenous or ipsilateral arm vein is a safe and effective strategy.

Influence of crural vessel run-off on short- and mid-term outcomes following femoro-popliteal bypass grafting.

OBJECTIVES: To determine the influence that the number of patent crural run-off vessels has on short- and mid-term outcomes following femoro-popliteal bypass. METHODS: All patients undergoing index femoro-popliteal bypass grafting between 2013 and 19 at our unit were included. Preoperative imaging was used to stratify patients into cohorts with either one or ≥2 patent run-off vessels. Primary outcomes measures included bypass patency and limb salvage rates at one and 3 years post-operatively. Survival analysis was performed using Kaplan-Meier curves and Logrank test. RESULTS: 147 bypasses performed on 143 patients were included. 24 patients had one-vessel run-off and 123 had ≥2 vessels patent. Patients with one-vessel run-off had a higher proportion of emergency admissions (54% vs 41%) and diabetes (42% vs 31%). 31% of patients underwent diagnostic angiogram imaging in addition to having duplex ultrasound and/or computed tomography angiography. There were no significant differences in primary, primary-assisted or secondary patency rates between the cohorts at 12 or 36 months. Limb salvage rates were significantly higher amongst those with ≥2 vessel run-off at 12 (86% vs 71%, p = 0.03) and 36 (85% vs 71%, p = 0.04) months. For those with occluded grafts, a higher proportion of patients with ≥2 vessel run-off subsequently had an attempt at redo bypass grafting. CONCLUSIONS: Femoro-popliteal bypass is a reasonable treatment option for patients with one-vessel run-off. However, whilst patency rates are comparable, clinicians should be aware of the lower successful limb salvage rates for patients with one patent vessel (especially those presenting with tissue loss).

The comparison of the short and mid-term results of endovascular interventions and bypass graft surgery in the treatment of patients with intermittent claudication complaints because of isolated femoropopliteal artery disease.

BACKGROUND: Intermittent Claudication (IC) is exercise pain seen in lower extremity arterial diseases. If it is left untreated, it may be the initial sign of a process leading to amputation. In the present study, the purpose was to compare the postoperative early and mid-term results of the patients who were treated with endovascular methods and those who underwent bypass graft surgery in the treatment due to IC complaints because of isolated Femoropopliteal Arterial Disease. METHOD: Postoperative first-month, sixth-month, and 12th-month follow-up results, procedure requirements, and demographic characteristics of the 153 patients who underwent femoropopliteal bypass because of isolated Femoropopliteal Arterial Disease and 294 patients who underwent endovascular intervention in our hospital between January 2015 and May 2020 were compared in the study. RESULTS: It was found in demographic characteristics that endovascular intervention was performed more frequently in smokers and graft bypass surgery was performed more frequently in hyperlipidemic patients, and the results were found to be statistically significant. High amputation rates were detected at statistically significant levels in diabetic and hypertriglycemic patients and 1-year primary patency rates were found to be higher in patients who underwent graft bypass surgery. No differences were detected between the two methods in terms of mortality. CONCLUSION: Interventional treatment modalities must be considered for patients with isolated Femoropopliteal Arterial Disease whose symptoms persist despite exercise and the best medical treatment. We think that Bypass Graft Surgery has more positive results than endovascular interventions when short and medium-term amputation, repetitive intervention needs, and changes in quality of life are compared in patients who receive the same medical treatment.

Pre-clinical In Vitro Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) is a feared complication. Prevention is of the utmost importance and vascular graft coatings (VGCs) could offer a potential to do this, with in vitro research a first crucial step. The aim of this study was to summarise key features of in vitro models investigating coating strategies to prevent VGI in order to provide guidance for the setup of future translational research. DATA SOURCES: A comprehensive search was performed in MEDLINE, Embase, and Web of Science. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). In vitro models using a VGC and inoculation of the graft with a pathogen were included. The type of graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 45 papers met the inclusion criteria. The majority used polyester grafts (68.2%). Thirty-one studies (68.9%) included antibiotics, and nine studies (20%) used a commercial silver graft in their protocol. New antibacterial strategies (e.g., proteolytic enzymes) were investigated. A variety of testing methods was found and focused mainly on bacterial adherence, coating adherence and dilution, biofilm formation, and cytotoxicity. Ninety-three per cent of the studies (n = 41) were considered unreliable. CONCLUSION: Polyester is the preferred type of graft to coat on. The majority of coating studies are based on antibiotics; however, new coating strategies (e.g., antibiofilm coating) are coming. Many in vitro setups are available. In vitro studies have great potential, they can limit the use, but cannot replace in vivo studies completely. This paper can be used as a guidance document for future in vitro research.

Ipsilateral carotid bypass outcomes in hostile neck anatomy.

OBJECTIVE: To determine differences in outcomes among patients undergoing ipsilateral carotid bypass with hostile or normal neck anatomy. METHODS: Single-center retrospective review of all ipsilateral extracranial carotid bypasses performed between 1998 and 2018. RESULTS: Forty-eight patients underwent ipsilateral carotid bypass from the common carotid artery to either the internal carotid artery or carotid bifurcation during the study period. Seven patients were excluded owing to either a lack of follow-up or missing data. The indications for intervention included infected patches, aneurysmal degeneration, symptomatic and asymptomatic stenosis or restenosis, carotid body tumors, neck malignancy, and trauma. In 25 procedures (61%), there was a hostile neck anatomy defined as a prior history of external beam neck irradiation or neck surgery. Among this group, 12 pectoralis muscle flaps were performed for reconstructive coverage. Conduits included polytetrafluorethylene (n = 21), great saphenous vein (n = 9), superficial femoral artery (n = 7) and arterial homograft (n = 4). All superficial femoral artery conduits were used in the hostile neck group (P = .03). The overall mean time of follow-up was 22 months, with all bypasses remaining patent with no significant clinical stenosis. The 30-day ipsilateral stroke and myocardial infarction rates were 4.88% each, all within the hostile neck group, with no 30-day mortalities for the entire cohort. One-third of the muscle flaps were performed in the setting of infected patches (P = .02) with no significant differences in perioperative outcomes with use. The overall median hospital length of stay was significantly increased in patients receiving muscle flap coverage (3.0 vs 7.0 days; P = .04). CONCLUSIONS: In patients with a complex carotid pathology, ipsilateral carotid bypass is an effective solution for carotid reconstruction. Different conduits should be used depending on the indication. Muscle flap coverage should be considered in hostile settings when primary wound closure is not feasible.

Appraising 5 years in activity of the largest public Canadian vascular graft bank.

BACKGROUND: In Canada, tissue distribution is managed by provincial entities. In 2014, Hema-Quebec established a cryopreserved vascular tissue bank accessible to all Canadian hospitals. The objectives of this report were to review the first 5 years of activity of Hema-Quebec's vascular bank and to briefly assess the competitiveness of its products. METHODS: Deceased donors, ages 15 to 60, were screened for common blood-borne diseases. Grafts were treated in a triple-antibiotic solution at 35°C before preservation at -100°C. Hema-Quebec's vascular graft records were analyzed from 2014 to 2019 inclusively. RESULTS: The average donor age was 35 years old and 78% of donors were men. Overall, 63% of harvested grafts cleared the quality management system. Positive microbial cultures and morphologic defects were the major reasons for graft discard. As such, a total of 60 grafts were delivered between 2016 and 2019 to 8 hospital centers. Moreover, the bank achieved a mean activity increase of 55% per year and Hema-Quebec's homografts were 48% less costly compared with similar homographs from for-profit organizations. CONCLUSIONS: Our findings demonstrate that Hema-Quebec has established a viable cryopreserved vascular tissue bank with steady increase in activity and an acceptable graft discard rates and pricing. Based on our findings, we recommend that efforts should be directed to expand the tissue bank graft distribution outside the province of Quebec.

Pre-clinical in vivo Models of Vascular Graft Coating in the Prevention of Vascular Graft Infection: A Systematic Review.

OBJECTIVE: Vascular graft infection (VGI) remains an important complication with a high mortality and morbidity rate. Currently, studies focusing on the role of vascular graft coatings in the prevention of VGI are scarce. Therefore, the aims of this study were to survey and summarise key features of pre-clinical in vivo models that have been used to investigate coating strategies to prevent VGI and to set up an ideal model that can be used in future preclinical research. DATA SOURCES: A systematic review was conducted in accordance with the Preferred reporting items for Systematic Reviews and Meta-Analysis guidelines. A comprehensive search was performed in MEDLINE (PubMed), Embase, and Web of Science. REVIEW METHODS: For each database, a specific search strategy was developed. Quality was assessed with the Toxicological data Reliability Assessment Tool (ToxRTool). The type of animal model, graft, coating, and pathogen were summarised. The outcome assessment in each study was evaluated. RESULTS: In total, 4 667 studies were identified, of which 94 papers focusing on in vivo testing were included. Staphylococcus aureus was the organism most used (n = 65; 67.7%). Most of the graft types were polyester grafts. Rifampicin was the most frequently used antibiotic coating (n = 43, 48.3%). In the outcome assessment, most studies mentioned colony forming unit count (n = 88; 91.7%) and clinical outcome (n = 72; 75%). According to the ToxRTool, 21 (22.3%, n = 21/94) studies were considered to be not reliable. CONCLUSION: Currently published in vivo models are very miscellaneous. More attention should be paid to the methodology of these pre-clinical reports when transferring novel graft coatings into clinical practice. Variables used in pre-clinical reports (bacterial strain, duration of activity coating) do not correspond well to current clinical studies. Based on the results of this review, a proposal for a complete and comprehensive set up for pre-clinical invivo testing of anti-infectious properties of vascular graft coatings was defined.

The role of surgical and total endovascular techniques in the treatment of ruptured juxtarenal aortic aneurysms.

Background: Ruptured juxtarenal aortic aneurysms (RJAAA) represent a special challenge in clinical practice, but the evidence to guide therapeutic decision-making is scarce. The aim of this study was to present two different approaches, open surgical (OAR) and chimney endovascular repair (CHEVAR), for treating patients with RJAAA. Patients and methods: This retrospective two-center study included all patients per center undergoing OAR or CHEVAR for RJAAA between February 2008 and January 2020. Juxtarenal aortic aneurysms were defined as having an infrarenal neck of 2-5 mm, measured after three-dimensional reconstruction of the computed tomography angiography scan. Results: 12 OAR patients (10 male, median age 73 years [58-90 years]) and 6 CHEVAR patients (all male, median age 74 years [59-83 years]) were included. In the OAR group, the proximal aortic clamping was suprarenal in 7 and interrenal in 5 patients. Cold renal perfusion was used in 4 patients, in 2 with suprarenal aortic clamping and in 2 with interrenal aortic clamping. 3 CHEVAR patients received a single renal chimney, the other 3 received double renal chimneys. Technical success was 12/12 in the OAR group 5/6 in the CHEVAR group. In-hospital mortality and 30-day mortality were 3/12 after OAR and 0/6 after CHEVAR. 2 OAR patients required transient dialysis. Median in-hospital stay was 14 (10-63) and 8 (6-21) days and median follow-up (FU) was 20 (3-37) and 30 (7-101) months, respectively. No further deaths occurred during FU. One OAR patient and 4 CHEVAR patients required aortic reinterventions. Conclusions: RJAAAs are rare. Both OAR and CHEVAR can represent adequate treatments for RJAAAs. OAR is the traditional approach, but CHEVAR has - in a high-volume center - promising early results with nonetheless a need for continuous FU to prevent reinterventions. Defining the studied aortic pathology precisely is essential for future research in order to draw valid conclusions.

Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo.

Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. Decellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and confirmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day -7 to 28). Likewise, we found no difference in systemic inflammatory and anti-inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro-inflammatory response further supporting its use as a TEVG in an allogeneic setup.

Potential of mesenchymal stem cells for bioengineered blood vessels in comparison with other eligible cell sources.

Application of stem cells in tissue engineering has proved to be effective in many cases due to great proliferation and differentiation potentials as well as possible paracrine effects of these cells. Human mesenchymal stem cells (MSCs) are recognized as a valuable source for vascular tissue engineering, which requires endothelial and perivascular cells. The goal of this review is to survey the potential of MSCs for engineering functional blood vessels in comparison with other cell types including bone marrow mononuclear cells, endothelial precursor cells, differentiated adult autologous smooth muscle cells, autologous endothelial cells, embryonic stem cells, and induced pluripotent stem cells. In conclusion, MSCs represent a preference in making autologous tissue-engineered vascular grafts (TEVGs) as well as off-the-shelf TEVGs for emergency vascular surgery cases.

Novel bypass risk predictive tool is superior to the 5-Factor Modified Frailty Index in predicting postoperative outcomes.

OBJECTIVE: This study aimed to develop risk predictive models of 30-day mortality, morbidity, and major adverse limb events (MALE) after bypass surgery for aortoiliac occlusive disease (AIOD) and to compare their performances with a 5-Factor Frailty Index. METHODS: The American College of Surgeons National Surgical Quality Improvement Program 2012-2017 Procedure Targeted Aortoiliac (Open) Participant Use Data Files were queried to identify all patients who had elective bypass for AIOD: femorofemoral bypass, aortofemoral bypass, and axillofemoral bypass (AXB). Outcomes assessed included mortality, major morbidity, and MALE within 30 days postoperatively. Major morbidity was defined as pneumonia, unplanned intubation, ventilator support for >48 hours, progressive or acute renal failure, cerebrovascular accident, cardiac arrest, or myocardial infarction. Demographics, comorbidities, procedure type, and laboratory values were considered for inclusion in the risk predictive models. Logistic regression models for mortality, major morbidity and MALE were developed. The discriminative ability of these models (C-indices) were compared with that of the 5-Factor Modified Frailty Index (mFI-5): a general frailty tool determined from diabetes, functional status, history of chronic obstructive pulmonary disease, history of congestive heart failure, and hypertension. Calculators were derived using the most significant variables for each of the three risk predictive models. RESULTS: A total of 2612 cases (mean age 65.0, 60% male) were identified, of which 1149 (44.0%) were femorofemoral bypass, 1138 (43.6%) were aortofemoral bypass, and 325 (12.4%) were axillofemoral bypass. Overall, the rates of mortality, major morbidity, and MALE were 2.0%, 8.5%, and 4.9%, respectively. Twenty preoperative risk factors were considered for incorporation in the risk tools. Apart from procedure type, age was the most statistically significant predictor of both mortality and morbidity. Preoperative anemia and critical limb ischemia were the most significant predictors of MALE. All three constructed models demonstrated significantly better discriminative ability (P < .001) on the outcomes of interest as compared with the mFI-5. CONCLUSIONS: Our models outperformed the mFI-5 in predicting 30-day mortality, major morbidity, and adverse limb events in patients with AIOD undergoing elective bypass surgery. Calculators were created using the most statistically significant variables to help calculate individual patient's postoperative risks and allow for better informed consent and risk-adjusted comparison of provider outcomes.

Climatic influence on the risk of abdominal aortic aneurysm rupture.

Our aim is to examine the effects of climatic conditions on the incidence of ruptured abdominal aortic aneurysms (rAAA) in Catalonia, Spain. We combined clinical data from the Public Health official registries in Catalonia, Spain (HD-MBDS) of all rAAA with local climatic data obtained from the closest meteorological station (69 stations, National Meteorological Service: MeteoCat) from 2008 to 2017. We analyzed the median, maximum, minimum, and variability of atmospheric pressure (hPa) and air temperature (°C), solar irradiation (MJ/m2), humidity (%), accumulated precipitation (mm), median wind, and maximum flaw direction and velocity (°, m/s), recorded on the days of events, the previous day, and mean results for 3, 7, and 30 days before, as well as seasonality. Seventy-five control days were randomly selected in a 1-year period around every rAAA day at the same meteorological station, and compared. A total of 717 days and locations with rAAA were identified, and 53,775 controls were randomly selected. For the rAAA days, there were significantly lower temperatures, lower solar global irradiation, and higher mean humidity levels in all time periods (p < 0.001, p < 0.001, p < 0.05); higher atmospheric pressure variability during 1 week and 1 month before (p = 0.011, p = 0.007); and they often occurred during autumn/winter (57.6%, p < 0.001). Logistic regression identified low mean temperatures on the days of ruptures and high mean humidity the week before as independent rupture predictors. In conclusion, low median temperatures the same day and high humidity during 1 week before were identified as independent predictors of rAAA occurrence. The role of climate on pathophysiologic mechanisms may require further investigation.

Rapid Self-Assembly of Bioengineered Cardiovascular Bypass Grafts From Scaffold-Stabilized, Tubular Bilevel Cell Sheets.

BACKGROUND: Cardiovascular bypass grafting is an essential treatment for complex cases of atherosclerotic disease. Because the availability of autologous arterial and venous conduits is patient-limited, self-assembled cell-only grafts have been developed to serve as functional conduits with off-the-shelf availability. The unacceptably long production time required to generate these conduits, however, currently limits their clinical utility. Here, we introduce a novel technique to significantly accelerate the production process of self-assembled engineered vascular conduits. METHODS: Human aortic smooth muscle cells and skin fibroblasts were used to construct bilevel cell sheets. Cell sheets were wrapped around a 22.5-gauge Angiocath needle to form tubular vessel constructs. A thin, flexible membrane of clinically approved biodegradable tissue glue (Dermabond Advanced) served as a temporary, external scaffold, allowing immediate perfusion and endothelialization of the vessel construct in a bioreactor. Subsequently, the matured vascular conduits were used as femoral artery interposition grafts in rats (n=20). Burst pressure, vasoreactivity, flow dynamics, perfusion, graft patency, and histological structure were assessed. RESULTS: Compared with engineered vascular conduits formed without external stabilization, glue membrane-stabilized conduits reached maturity in the bioreactor in one-fifth the time. After only 2 weeks of perfusion, the matured conduits exhibited flow dynamics similar to that of control arteries, as well as physiological responses to vasoconstricting and vasodilating drugs. The matured conduits had burst pressures exceeding 500 mm Hg and had sufficient mechanical stability for surgical anastomoses. The patency rate of implanted conduits at 8 weeks was 100%, with flow rate and hind-limb perfusion similar to those of sham controls. Grafts explanted after 8 weeks showed a histological structure resembling that of typical arteries, including intima, media, adventitia, and internal and external elastic membrane layers. CONCLUSIONS: Our technique reduces the production time of self-assembled, cell sheet-derived engineered vascular conduits to 2 weeks, thereby permitting their use as bypass grafts within the clinical time window for elective cardiovascular surgery. Furthermore, our method uses only clinically approved materials and can be adapted to various cell sources, simplifying the path toward future clinical translation.

Increased warm ischemia time during vessel harvest decreases the primary patency of cryopreserved conduits in patients undergoing lower extremity bypass.

OBJECTIVE: Autologous vein is the preferred conduit for lower extremity bypass. However, it is often unavailable because of prior harvest or inadequate for bypass owing to insufficient caliber. Cryopreserved cadaveric vessels can be used as conduits for lower extremity revascularization when autogenous vein is not available and the use of prosthetic grafts is not appropriate. Many studies have shown that donor characteristics influence clinical outcomes in solid organ transplantation, but little is known regarding their impact in vascular surgery. The purpose of this study was to examine the effects donor variables have on patients undergoing lower extremity bypass with cryopreserved vessels. METHODS: The tissue processing organization was queried for donor blood type, warm ischemia times (WITs), and serial numbers of cryopreserved vessels implanted at a single center from 2010 to 2016. The serial numbers were then matched with their respective patients using the institutional Clinical Data Repository and patient data were obtained from the Clinical Data Repository and chart review. Primary outcomes were primary patency of the bypass conduits and limb salvage. Time to loss of patency was evaluated using Kaplan-Meier methods and a Cox proportional hazards model determined risk-adjusted predictors of patency and limb salvage. RESULTS: Sixty patients underwent lower extremity bypass with 65 cryopreserved vessels (23 superficial femoral arteries, 41 saphenous veins, 1 femoral vein). Thirty-eight procedures were reoperations. There were 21 inflow, 44 outflow, and 44 infrainguinal procedures. Preexisting comorbidities did not differ significantly between those who lost patency and those who did not. The mean WIT among the entire cohort was 892.3 ± 389.1 minutes (range, 158.0-1434.0 minutes). The median follow-up was 394 days. Kaplan-Meier analysis demonstrated an overall 1-year primary patency rate of 51%. Primary patency at 1 year was 67% and 41% for inflow and outflow procedures, respectively, and did not differ significantly between the two groups (P = .15). Donor-to-recipient ABO incompatibility was not associated with loss of primary patency. The 1-year amputation-free survival was 74%. Primary patency significantly decreased with each hourly increase in WIT on risk-adjusted analysis (hazard ratio, 1.1; P = .02). CONCLUSIONS: Higher cryopreserved vessel WIT was associated with increased risk-adjusted loss of primary patency in this cohort. At 1 year, the overall primary patency was 51% and amputation-free survival was 74%. Vascular surgeons should be aware that WIT may affect outcomes for lower extremity bypass.